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128 Free Radical Biomedicine: Principles, Clinical Correlations, and Methodologies Y. Robert Li
5.4. Spinal Cord Injury
5.5. Drug/Xenobiotic-Induced Neurotoxicity
6. REFERENCES
1. OVERVIEW
The human nervous system is the site of consciousness, cognition, and behavior; as such it is the most intricate
structure known to exist. About one third of the genes encoded in the human genome are expressed in the
nervous system. It is estimated that each mature human brain consists approximately 100 billion neurons,
several million miles of axons and dendrites, and over 10 15 synapes. Neurons exist within a dense parenchyma
of multifunctional glial cells that synthesize myelin, preserve homeostasis, and regulate immunity and
inflammation. The extreme complex structure and functionality of the nervous system make it a vulnerable
target of both exogenous and endogenous pathophysiological factors. There are numerous types of neurological
diseases, and the common ones worldwide include (in alphabetic order) dementia (e.g., Alzheimer’s disease),
epilepsy, headache disorders, multiple sclerosis, neuroinfections, neurological disorders associated with
malnutrition, pain associated with neurological disorders, Parkinson’s disease, stroke, and traumatic brain
injury. Neurological diseases kill an estimated 6.8 million people each year, equating to 12% of global deaths.
Neurological diseases are also common and costly in the United States. An estimated 180 million Americans
suffer from a neurological disease, resulting in an annual cost of over 700 billion dollars.
As the global population ages, the impact of neurological diseases in both developed and developing countries
will increase. Hence, developing effective public health strategies and therapeutic modalities are essential for
combating these disorders of increasing global public health importance. Studies over the last several decades
have resulted in a great understanding of the pathophysiology of many neurological diseases, which provides a
basis for the development of drugs for both preventive and therapeutic intervention of these diseases. In this
context, accumulating evidence supports a critical role for free radicals and related reactive species in the
pathophysiological processes of many common and rare neurological diseases. This chapter summarizes the
key findings from both experimental models and human studies, highlighting oxidative stress as an important
pathophysiological component of various types of neurological diseases, including stroke, Alzheimer’s disease,
Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, traumatic brain injury, spinal cord
injury, and drug/xenobiotic-induced neurotoxicity. The antioxidant-based intervention of these neurological
diseases is also discussed in the chapter.
2. FREE RADICALS AND RELATED REACTIVE SPECIES IN STROKE
2.1. Introduction to Stroke
2.1.1. Definition and Epidemiology
The term cerebral vascular disease refers to disorders of the vasculature of the central nervous system. A
stroke or cerebrovascular accident is defined as an abrupt onset of a neurological deficit that occurs as a
result of either inadequate blood flow (ischemic stroke) or hemorrhage into the brain tissue (parenchymal or
intracerebral hemorrhage) or surrounding subarachnoid space (subarachnoid hemorrhage). Focal ischemic
stroke is usually caused by thrombosis of the cerebral vessels themselves or by emboli from a proximal
arterial source or the heart. Focal ischemic stroke (often simply referred to as ischemic stroke) accounts for
87% of all cases. A generalized reduction in cerebral blood flow due to systemic hypotension (e.g.,
cardiogenic shock) usually produces syncope, and in more severe instances, results in hypoxic-ischemic
encephalopathy. This condition is, however, not classified as stroke. Another condition related to cerebral
ischemia is transient ischemic attack (TIA). A TIA is a transient episode of neurological dysfunction caused
by focal brain, spinal cord, or retinal ischemia, without acute infarction [1]. Patients with TIAs are at high
risk of early stroke. Table 6.1 lists the classification of stroke.